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Biomedical subjects

H Noguchi

Publications and source records attributed to H Noguchi.

At least 235 records · Page 13Linked to original sources

Sarcoidosis accompanied by pancreatic impairment.

A 64-year-old male complained of weight loss and slight fever. Bilateral hilar lymphadenopathy and hepato-splenomegaly were observed. Serum ACE level was high, and liver function was impaired. Laparoscopy demonstrated small white nodules on the liver surface. A definite diagnosis of sarcoidosis was made by histological study of the specimen by liver biopsy and noncaseating epithelioid cell granulomas composed of giant cells and epithelioid cells were revealed. Various pancreatic enzymes were increased on admission, suggesting pancreatic impairment due to sarcoidosis. Corticosteroid therapy improved liver and pancreatic functions and decreased splenomegaly. He has been followed up for 4 years and 5 months.

Humans↗

Prolonged dysequilibrium in three cases with vestibular neuronitis: efficacy of vestibular rehabilitation.

The clinical course of acute unilateral vestibular disturbance in 3 cases with vestibular neuronitis and a case with labyrinthine destruction was surveyed for a long-term period. Vestibular training with a modified Cawthorne-Cooksey's exercise was done in 2 of 3 cases with vestibular neuronitis and a case of labyrinthine destruction. All had no severe troubles in activities of their daily lives over one year after the onset of the disease, but the central compensation was not completed, even in a young patient, in a case of labyrinthine destruction and in a well trained case. Spontaneous nystagmus to the affected side and increase of body sway with eyes closed were revealed by examinations in all cases. Physical exercise was found to be effective for relief from vestibular ataxia, but it was difficult to keep the effect even after training.

Adult↗

Perinatal development of amine, alcohol and phenol sulfoconjugations in the rat.

Development of the sulfoconjugating activities for amine, alcoholic and phenolic compounds was studied in hepatic 105,000 g supernatants of fetal and newborn rats. All activities in the fetus at the late stage of pregnancy were negligible or very low when compared with those of the adult female level. Amine and alcohol sulfoconjugating activities were low 2 days after birth, increased with age, and attained the adult female level 17 days after birth. In contrast, phenol sulfoconjugating activity was nearly half the level of adult female rats in the neonates 2 days after birth and was relatively constant before maturation. There were no sex-related differences in any of the activities in the immature rats, but in adult animals the activities for amine and alcohol were higher in the females than in the males; the opposite was observed for phenol sulfoconjugation.

Age Factors↗

[Study of uneven pulmonary ventilation by sequential bolus method].

We report a new method of measuring the sequential ventilation associated with the primary mechanism for ventilation inhomogeneity. Four types of sequential curves were examined using simultaneous washouts of multiple tracer boluses inhaled from residual volume (RV) and at volumes above RV. The factors that affected the classification of curves were analyzed by the theory of quantification from the statistical data of blood gases, lung function tests, X-ray and clinical diagnosis. This method was applied to evaluate the ventilation distribution in 100 patients with pulmonary disease. It provided clinical information on certain types of disease which cannot be detected by traditional lung function tests. Sequential bolus method may permit determination of whether the disease has predominantly intra or inter-regional inhomogeneity.

Evaluation Studies as Topic↗

[A method for measurement of circulating blood volume with fluorescein isothiocyanate labeled red blood cells].

We developed a new method to measure the total circulating blood volume using fluorescein isothiocyanate (FITC) labeled autologous red blood cell as an indicator. Red blood cells were labeled by incubation with 0.1 mg.ml-1 FITC in PBS (pH 7.2) for 30 min at 37 degrees C. Eighteen dogs were given an intravenous injection of FITC labeled red blood cells, which were approximately 0.1% of the total circulating red blood cells estimated from the body weight. The ratio of labeled cells to the normal circulating red blood cells was determined by a flow cytometry. The total blood volume was calculated from its dilution rate. The average circulating blood volume determined by this method was 76.8 +/- 9.2 ml.kg-1 (mean +/- SD). This result coincides well with the values reported previously. This method using non radioactive tracers enables a reproducible measurement of circulating blood volume and its change with time.

Animals↗

[Complication of gastro-duodenum with intra-hepatic arterial infusion chemotherapy using implantable reservoir system for hepatic tumors].

The subjects were 20 cases with implantable reservoir systems for unresectable hepatic tumors. We evaluated the correlation between a complication of the gastro-duodenum after intra-hepatic arterial chemotherapy and a gastro-duodenal distribution of anti-cancer drugs using the hepatic perfusion scintigram by 99mTc-macroaggregated albumin via reservoirs. The 20 cases were divided into 3 groups (A, B, C) according to the level of gastro-duodenal accumulation of 99mTc-MAA. In group A with the strongest accumulation in the gastro-duodenum, we frequently found a gastro-duodenal ulcer after intra-hepatic arterial chemotherapy. There was a significant difference between group A and group C, the latter without a gastro-duodenal accumulation. These results suggested that the hepatic perfusion scintigram via reservoir was a useful examination to expect and prevent the complication of gastro-duodenum on intra-hepatic arterial infusion (especially continuous infusion) chemotherapy.

Carcinoma, Hepatocellular↗

Determination of gliclazide in serum by high-performance liquid chromatography using solid-phase extraction.

A simple and sensitive high-performance liquid chromatographic method for a routine assay of gliclazide in serum is described. Serum samples spiked with glibenclamide (internal standard) were applied to Bond Elut C18 cartridges. After washing with phosphate buffer (pH 7.5) and water, the cartridge was eluted with 60% methanol. The eluate was evaporated to dryness. The residue was dissolved in methanol and injected onto an octadecyl silica column (5 microns, 150 mm x 4.6 mm I.D.). The mobile phase was 0.04 M potassium dihydrogenphosphate (pH 4.6)-acetonitrile-isopropyl alcohol (5:4:1, v/v). Ultraviolet detection at 227 nm was used. The minimum detectable level of gliclazide was 20 ng/ml.

Chromatography, High Pressure Liquid↗

13C-NMR spectral analysis of the structures of mouse immunoglobulin G1 carrying allotypes a and j.

A novel 13C nuclear magnetic resonance (NMR) method is described for the detection of subtle structural differences between mouse immunoglobulins carrying different allotypes. Fc fragments of mouse IgG1 antibodies carrying allotypes a and j have been selectively labeled with [1-13C]methionine. 13C-NMR spectra have shown that the microenvironment around Met-398 is significantly different for the two kinds of allotypes. Peptide mapping and amino acid sequence analyses have revealed that Val-406 of IgG1 carrying allotype a is substituted for Ile in the case of allotype j. X-ray crystallographic data indicate that Met-398 is in close spatial proximity to Val (Ile)-406. We therefore conclude that the 13C-NMR method can provide us with a novel spectroscopic probe for the structural characterization of allotypic markers.

Amino Acid Sequence↗

Monoclonal antibodies against Pseudomonas aeruginosa elastase: a neutralizing antibody which recognizes a conformational epitope related to an active site of elastase.

We have established seven murine hybridoma cell lines which produce monoclonal antibodies (mAbs) against Pseudomonas aeruginosa elastase. The seven mAbs recognized at least six different epitopes on the elastase molecule. All mAbs inhibited both enzymatic activities of elastase and protease, in which elastin fluorescein and hide powder azure were used as substrates, respectively. One of them, mAb E-4D3, strongly neutralized enzymatic activities of peptidase in which furylacryloyl-glycyl-leucinamide was used as a substrate, as well as of elastase and protease. In contrast, the other six mAbs did not neutralize peptidase activity at all. The Ki value for furylacryloyl-glycl-leucinamide of E-4D3, as well as its Fab fragment, was comparable to those for metalloprotease inhibitors such as phosphoramidon and Zincov inhibitor. The binding of mAb E-4D3 was inhibited by phosphoramidon and Zincov inhibitor, but not by metal chelators such as EDTA and o-phenanthroline. A line of evidence suggests that mAb E-4D3 directly interacts with active site and highly neutralizes enzymatic activity of P. aeruginosa elastase. Data of Western blotting and ELISA suggest that mAb E-4D3 is likely to recognize an elastase molecule in a conformation-dependent manner as an epitope. In contrast, the neutralizing activity of the other mAbs against elastase and protease seems to be caused by a low accessibility of an enzyme to insoluble and high-molecular-mass substrates through the binding and steric hindrance of the mAbs to an enzyme.

Amino Acid Sequence↗

Determination of nadolol in serum by high-performance liquid chromatography with fluorimetric detection.

A sensitive high-performance liquid chromatographic method for a routine assay of nadolol in serum is described. Serum samples spiked with atenolol (internal standard) were extracted with diethyl ether. After centrifugation, the organic layer was evaporated to dryness. The residue was redissolved in the mobile phase and injected onto an octadecyl silica column (150 mm x 4.6 mm I.D.). The mobile phase was 0.05 M ammonium acetate (pH 4.5)-acetonitrile (85:15, v/v). Fluorometric detection (excitation 230 nm, emission 300 nm) was used. The minimum detectable level of nadolol in serum was 1 ng/ml.

Atenolol↗

Endorectal pull-through operation for diffuse cavernous hemangiomatosis of the sigmoid colon, rectum and anus.

A 6-year-old girl with diffuse cavernous hemangiomatosis of the sigmoid colon, rectum and anus underwent endorectal pull-through operation for sphincter-saving resection. Rectal mucosa was resected from 4 cm above peritoneal reflection to anal skin margin and the normal sigmoid colon was pulled down through the rectal muscular cuff. Ligation of the superior rectal and left internal iliac arteries at operation achieved satisfactory control of bleeding. Postoperative manometric studies showed almost normal sphincter tone and good response to rectal stimuli by balloon inflation. The endorectal pull-through (Soave-Denda procedure) is a common procedure for Hirschsprung's disease and the best procedure for the sphincter-saving treatment of diffuse cavernous hemangiomatosis of the colon and rectum.

Anal Canal↗

Morphological and functional changes of islets of Langerhans in FK506-treated rats.

FK506, a new immunosuppressant, caused glucose intolerance in rats given daily oral doses of 1, 5, or 10 mg/kg/day for 14 days, but did not induce hyperglycemia under normal feeding. Besides the glucose intolerance, insulin secretion was impaired and insulin levels in the pancreas were lowered. Histopathologically, there was vacuolation of the Langerhans islets in the animals given 10 mg/kg. After withdrawal of the drug, these changes in pancreatic function and morphology returned to normal within 2 weeks. The findings indicate that FK506 caused dose-dependent but reversible islet toxicity in rats.

Animals↗

The effects of FK506 and cyclosporine on the exocrine function of the rat pancreas.

The effects of FK506 on exocrine function of the pancreas in Sprague-Dawley rats were examined and compared with those of cyclosporine. FK506 did not affect the levels of amylase and lipase in the pancreas of rats given the drug orally in a daily dose of 1 or 5 mg/kg for 2 weeks. Furthermore, the pancreas of the rats showed good exocrine secretion of enzymes such as amylase and lipase on stimulation with carbachol in vitro. Cyclosporine 50 mg/kg given in the same way as FK506 also was free of effect on enzyme levels in the rat pancreas, but the exocrine secretion of the enzyme from the pancreatic lobules on stimulation with carbachol was impaired. It is concluded that FK506 does not affect pancreatic exocrine function in rats.

Amylases↗

Variable cross-reactivity of Pseudomonas aeruginosa lipopolysaccharide-code-specific monoclonal antibodies and its possible relationship with serotype.

The core region of Pseudomonas aeruginosa lipopolysaccharide (LPS) was analysed by four LPS-core-specific human monoclonal antibodies (mAbs; FK-2E7, MH-4H7, OM-1D6 and NM-3G8). Reactivity of these mAbs to about 180 P. aeruginosa strains was tested. FK-2E7 bound to strains of Homma serotype E and I at a frequency of about 90%, to strains of serotype M at about 50%, and to strains of serotype A and G at about 30%. MH-4H7 bound to P. aeruginosa strains of serotype A, F, G, H, K and M at a high frequency (45-87%), but did not bind to any strains of serotype B, C, E and I. OM-1D6 and NM-3G8 bound to P. aeruginosa strains in a nearly serotype-specific manner. OM-1D6 reacted with all strains of serotype G so far tested, and a few strains of serotype M. Furthermore, L-rhamnose in the LPS core of serotype G was an immunodominant sugar recognized by OM-1D6 as an epitope. NM-3G8 bound to only a few strains of serotype B and M. The variable reactivity of these mAbs suggests that antigenic heterogeneity of the LPS core is somewhat related with (O-polysaccharide-based) serotype. Among these mAbs, MH-4H7 and OM-1D6 showed a high level of protective activity against P. aeruginosa in an experimental infection model using normal mice. In vivo protective activity was shown to be closely related to in vitro binding activity to whole cells as determined by agglutination and flow cytometry, but not ELISA.

Agglutination Tests↗

Temperature-sensitive immunoglobulin A-binding and dimerization of C-terminus-impaired protein Arp4 produced in Escherichia coli.

A gene for protein Arp4, an IgA receptor protein derived from Streptococcus pyogenes AP4, was expressed in Escherichia coli. The product was demonstrated to be accumulated in a periplasmic space as a polypeptide with an apparent molecular weight of 40 kDa with the deleted C-terminal membrane anchor portion of protein Arp4. This 40-kDa peptide of the C-terminus-impaired recombinant protein Arp4 produced in E. coli, designated ir-protein Arp4, was purified from a periplasmic fraction of transformants and its IgA-binding activity was analyzed. The IgA binding of ir-protein Arp4 was temperature-sensitive, that is, ir-protein Arp4 bound IgA at 4 and 25 C, but did not at 37 C. In addition, the dimerization of ir-protein Arp4 was also temperature-sensitive in parallel with temperature-dependent binding activity, suggesting that the dimerization of ir-protein Arp4 may be required for its active binding to IgA. In contrast, ir-protein Arp4 immobilized on Sepharose 4B did bind to IgA even at 37 C as well as 4 and 25 C. The immobilized ir-protein Arp4 might acquire the temperature-resistant IgA binding activity in part through the formation of a stable dimerized ir-protein Arp4 on the solid support.

Bacterial Proteins↗

Effects of a human antiflagellar monoclonal antibody in combination with antibiotics on Pseudomonas aeruginosa infection.

The in vivo activity of human immunoglobulin M monoclonal antibody IN-2A8, which is specific for flagellum type b of Pseudomonas aeruginosa, was evaluated in comparison to anti-O antigen (serotype B) MAb KO-2F2 and in combination with antibiotics. IN-2A8 showed stronger activity than KO-2F2 against subcutaneous infection in burned mice, while it was much less active against intraperitoneal infection in normal mice. In a burn infection model, IN-2A8 inhibited the increase of bacteria in skin lesions weakly and that in blood significantly, suggesting that it strongly suppressed bacterial spread to blood. The activity of IN-2A8 in combination with 10 antipseudomonal antibiotics against intraperitoneal infection was examined. Clear additive effect was observed with a combination of either carbapenem or aminoglycoside antibiotics in terms of mouse survival. The administration of an antibiotic, imipenem-cilastatin, simultaneously with or before that of IN-2A8 gave a combined effect, but the reverse order did not. The combination of IN-2A8 with imipenem-cilastatin decreased numbers of viable bacteria in the peritoneal cavity and blood and kept them low for a longer time than did either treatment alone. These results suggest that an antiflagellar monoclonal antibody would be effective against systemic infection in combination with some kinds of antibiotics.

Animals↗

Binding of monoclonal antibody specific for domain Ia/II of Pseudomonas aeruginosa exotoxin A at pH 4 strongly neutralizes exotoxin A-induced cytotoxicity in cell culture and in vivo.

Mouse monoclonal antibodies (MAbs) against Pseudomonas aeruginosa exotoxin A (Ex-A) were established, and 4 of 20 MAbs were extensively studied for analysis of the structure-function relationship of Ex-A. IN vivo experiments demonstrated that MAb Ex-3C7 protected mice either injected with Ex-A or infected with Ex-A-producing P. aeruginosa from death caused by Ex-A at the highest rate, followed by MAbs Ex-4F2 and Ex-8H5, in that order. MAb Ex-2A10 failed to rescue the mice. MAb Ex-3C7 (immunoglobulin G1 [IgG1]) inhibited incorporation of Ex-A into target cells and strongly neutralized cytotoxicity in cell culture but did not inhibit an enzymatic activity of Ex-A, ADP-ribosyltransferase, at all. The MAb also bound Ex-A, even at a low pH of 4, and recognized amino acid residues 241 to 297 (domain Ia/II), suggesting that MAb Ex-3C7 can interfere with the conformational change and/or processing of Ex-A by keeping a complex of Ex-A and antibody stable at low pH in the phagolysosome. MAb Ex-4F2 (IgG1), which recognizes residues 550 to 590 (domain III), strongly inhibited Ex-A incorporation and neutralized cytotoxicity in cell culture but only weakly inhibited ADP-ribosyltransferase. MAb Ex-8H5 (IgG1), which recognizes residues 591 to 613 (domain III), also inhibited cytotoxicity in cell culture, but weakly. In contrast to the above three MAbs, MAb Ex-2A10 (IgG2b) greatly inhibited ADP-ribosyltransferase but showed no inhibition of Ex-A incorporation and no neutralizing activity against cell toxicity. A line of evidence indicates that (i) domain Ia/II plays an important role in the pathogenesis of Ex-A and (ii) MAbs that inhibit an intracellular postbinding process, such as conformational change, processing, and translocation of Ex-A in target cells, can display potent inhibitory activity against cytotoxicity in vivo, as well as in cell culture, and would be a good candidate for therapy of pseudomonal infections.

ADP Ribose Transferases↗